Potassium Carbonate → 4-(4-Iodo-phenyl)-1-(3,3,3-trifluoro-propyl)-piperidine-4-carbonitrile
Reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:16][C:17]([F:22])([F:21])[CH2:18][CH2:19]Br.C([O-])([O-])=O.[K+].[K+]>CC#N.CCOC(C)=O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][N:11]([CH2:19][CH2:18][C:17]([F:22])([F:21])[F:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 60 °C
Procedure
To a solution of the crude 4-(4-iodo-phenyl)-piperidine-4-carbonitrile (0.60 g, ˜1.9 mmol) in CH3CN (6 mL) was added (3,3,3-trifluoro)-propyl bromide (1.02 mL, 9.6 mmol, 5 eq.) and K2CO3 (1.33 g, 9.6 mmol, 5 eq.) and the resulting mixture was stirred and heated to 60° C. for 16 h. The reaction was cooled to room temperature, diluted with EtOAc (20 mL) and washed with H2O (25 mL) and saturated brine (2×25 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to give the crude 4-(4-iodo-phenyl)-1-(3,3,3-trifluoro-propyl)-piperidine-4-carbonitrile as a red solid (0.761 g, 1.86 mmol, 98%). 1H NMR (300 MHz, CDCl3): δ 7.83 (dd, 2H), 7.33 (dd, 2H), 3.09 (d, 2H), 2.82 (dd, 2H), 2.66 (td, 2H), 2.45 (m, 2H), 2.18 (m, 4H); MS (ESI): 409.1/410.2 (M +1).
Workup
- temperatureThe reaction was cooled to room temperature
- washwashed with H2O (25 mL) and saturated brine (2×25 mL)
- dry with materialThe organic phase was dried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated by rotary evaporation
Sources & evidence
- ORD record
- ord-d558c4cb85864afbaf4583a1e036ba4a
- Source dataset
- uspto-grants-2005_05
- Patent number
- US06887889B2
Reaction notes
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